Paraneoplastic syndromes associated with lung cancer

Table 1 Criteria for the diagnosis of paraneoplastic endocrine syndromes

Abnormal endocrine function without physiologic feedback regulation

The absence of metastasis in the respective endocrine gland

Deterioration with increasing tumor burden

Improvement in endocrine function with the treatment of the tumor

Evidence of the presence of hormones in the tumor or hormone synthesis by the tumor

Table 2 Paraneoplastic endocrine syndromes and causes of hypercalcemia associated with lung cancer

Paraneoplastic endocrine syndromes associated with lung cancer

Humoral hypercalcemia of malignancy

Syndrome of inappropriate antidiuretic hormone production

Cushing’s syndrome

Hypoglycemia

Acromegaly

Carcinoid syndrome

Gynecomastia

Hyperthyroidism

Causes of hypercalcemia associated with lung cancer

Humoral hypercalcemia of malignancy

(1) Parathyroid hormone-related protein

(2) Parathyroid hormone

(3) 1,25-dihydroxyvitamin D

(4) Granulocyte colony-stimulating factor

Osteolytic activity at the sites of skeletal metastases

Table 3 Syndrome of inappropriate antidiuretic hormone secretion

Hyponatremia (serum sodium < 134 mEq/L)

Hypoosmolality (plasma osmolality < 275 mOsm/kg)

Inappropriately high urine osmolality ( > 500 mOsm/kg)

Inappropriately high urinary sodium concentration ( > 20 mEq/L)

Absence of hypothyroidism

Absence of adrenal insufficiency

Absence of volume depletion

Table 4 Classical and non-classical paraneoplastic neurological syndromes[93]

Syndromes of the central nervous system

Encephalomyelitis1

Limbic encephalitis1

Brainstem encephalitis

Subacute cerebellar degeneration1

Opsoclonus-myoclonus1

Optic neuritis

Cancer-associated retinopathy

Melanoma-associated retinopathy

Stiff person syndrome

Necrotizing myelopathy

Motor neuron diseases

Syndromes of the peripheral nervous system

Subacute sensory neuropathy1

Acute sensorimotor neuropathy

Guillain-Barre syndrome

Brachial neuritis

Subacute/chronic sensorimotor neuropathies

Neuropathy and paraproteinaemia

Neuropathy with vasculitis

Autonomic neuropathies

Chronic gastrointestinal pseudo-obstruction1

Acute pandysautonomia

Syndromes of the neuromuscular junction and muscle

Myasthenia gravis

Lambert-Eaton myasthenic syndrome1

Acquired neuromyotonia

Dermatomyositisa

Acute necrotizing myopathy

¹Classical syndromes.

Table 5 Onconeural antibodies

Well-characterized onconeural antibodies

Anti-Hu (ANNA1)

Anti-Yo (PCA1)

Anti-CV2 (CRMP5)

Anti-Ri (ANNA2)

Anti-Ma2 (Ta)

Anti-amphiphysin

Partially characterized onconeural antibodies

Anti-Tr (PCA-Tr)

ANNA3

PCA2

Anti-Zic4

Anti-mGluR1

Other antibodies

Anti-acetylcholine receptor

Anti-nicotinic AchR

Anti-voltage-gated calcium channel

Anti-voltage-gated potassium channel

Anti-NR1/NR2 of N-methyl-D-aspartate

Anti-glutamic acid decarboxylase

ANNA: Anti-neuronal nuclear antibodies.

Table 6 Criteria for the diagnosis of paraneoplastic neurological syndromes[93]

Definite PNS

A classical syndrome and cancer that develops within five years of the diagnosis of the neurological disorder

A non-classical syndrome that resolves or improves significantly after cancer treatment without concomitant immunotherapy, provided that the syndrome is not susceptible to spontaneous remission

A non-classical syndrome with onconeural antibodies (well characterized or not) and cancer that develops within five years of the diagnosis of the neurological disorder

A neurological syndrome (classical or not) with well-characterized onconeural antibodies and no cancer

Possible PNS

A classical syndrome, no onconeural antibodies, and no cancer, but a high risk of an underlying tumor

A neurological syndrome (classical or not) with partially characterized onconeural antibodies and no cancer

A non-classical syndrome, no onconeural antibodies, and cancer present within five years of the diagnosis

PNS: Paraneoplastic neurological syndromes.

Table 7 Criteria for the diagnosis of Lambert-Eaton myasthenic syndrome

Clinical features

(1) Proximal muscle weakness

(2) Autonomic symptoms

(3) Reduced tendon reflexes

Anti-voltage-gated calcium channel antibodies

Repetitive nerve stimulation abnormalities

(1) Low compound muscle action potential

(2) Decrease > 10% at low frequency (1-5 Hz)

(3) Increase > 100% after maximum voluntary contraction or at high frequency (50 Hz)

Table 8 Paraneoplastic dermatologic syndromes and paraneoplastic rheumatologic syndromes associated with lung cancer

Paraneoplastic dermatologic syndromes associated with lung cancer

Polymyositis/dermatomyositis

Acrokeratosis paraneoplastica (Bazex syndrome)

Acanthosis nigricans

Tripe palms

The sign of Leser-Trélat

Erythema gyratum repens

Cutaneous leukocytoclastic vasculitis

Pityriasis rubra pilaris

Rhinophyma

Eosinophilic cellulitis

Herperiformis pemphigus

Hypertrichosis lanuginose acquisita

Erythema elevatum diutinum

Paraneoplastic rheumatologic syndromes associated with lung cancer

Polymyositis/dermatomyositis

Vasculitis

Cutaneous leukocytoclastic vasculitis

Henoch-Schönlein purpura

Hypertrophic pulmonary osteoarthropathy

Remitting seronegative symmetrical synovitis with pitting edema

Polymyalgia rheumatica

Table 9 Criteria for the diagnosis of paraneoplastic glomerulopathy

No obvious alternative etiology other than malignancy

Existence of a time relationship between the diagnosis of glomerulopathy and malignancy

Clinical improvement after the complete surgical removal of the tumor or complete remission achieved by chemotherapy/radiotherapy

Deterioration of glomerulopathy associated with recurrence of the malignancy